Findings of the previous granting periods indicate that hemopoietic precursor cells are sensitive to in vivo chronic and acute benzene intoxication, using CFC and PFC assays. We shall further characterize the mechanism of toxicity on monocytic CFC by using an in vitro microsomal system (from liver or bone marrow) to activate benzene metabolites. Separation techniques will be employed to isolate these metabolites in order to determine their relative toxicity, in vitro. Complementary studies investigating the role of metabolism in benzene-induced hemopoietic toxicity will evaluate recovery mechanisms of hemopoiesis to benzene toxicity in mice treated with agents which alter the drug-metabolizing system. We shall also study the effects of chronic beneze exposure to erythrocytic precursor cells (using a clonal assay) and compare responses of these early erythrocytic cells with those of other hemopoietic precursor cell subsets, i.e., monocytic and lymphocytic pathways. We shall conduct studies (e.g., using B-cell markers) to further characterize the B-lymphocytic precursor cell population measured by the P-PFC assay, which we found to be sensitive to chronic benzene toxicity.